Precursor cells have become a central interest in medical research. Many tissues in the body have a back-up reservoir of precursors that can replace cells that are senescent or damaged by injury or disease. Considerable effort has been made recently to isolate precursors of a number of different tissues for use in regenerative medicine. Sources and systems for producing differentiated cells from a stem cell population for use wherever a relatively homogenous cell population is desirable have been summarized in for example U.S. patent application US2003/0040111. Multi- and pluripotent embryonic stem (ES) cells as well as embryonic germ (EG) cells of mammals can be induced to differentiate in culture into a variety of cell types, including cardiac muscle cells. However, ES cell-derived cardiomyocytes constitute only 1% to 5% of all cells in differentiated embryoid bodies (EBs). The large fraction of it is comprised of undifferentiated ES cells bearing significant tumorogenic potential.
Recently, genetic selection of specified cell types from differentiating cultures of embryonic stem (ES) cells based on the use of tissue-specific gene-regulatory elements—promoters driving a drug resistance cassette has been described; see, e.g., international application WO02/051987. Thus, the certain differentiated cell types originated from transgenic ES clones possessing the corresponding vector, could be selected by applying the corresponding drug that eliminates all other emerging cell types as well as undifferentiated ES cells. Up to date this approach has been proven as most specific and efficient for a high grade of purification of cardiac, neuronal and insulin-secreting cells from cultures of differentiating ES cells.
Nevertheless, a significant challenge to the use of stem cells for therapy is to control growth and differentiation into the particular type of tissue required for the treatment of each patient. Thus, there is a need for new approaches to generate populations of differentiated cells and tissues suitable for human administration. The solution to said technical problem is achieved by providing the embodiments characterized in the claims, and described further below.